ArticleNeuro-oncology2014
DNA methylation and gene deletion analysis of brain metastases in melanoma patients identifies mutually exclusive molecular alterations.
Open access · bronzeAbstract read
In one paragraph
Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.8field-weighted citation impact, top 5% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 87 citations in OpenAlex.
- Review
- Single-cell transcriptome analysis suggests cells of the tumor microenvironment as a major discriminator between brain and extracranial melanoma metastases.Biology direct · 2025Article
- The epigenetic landscape of brain metastasis.Oncogene · 2025Review
- Inflammasome activation in melanoma progression: the latest update concerning pathological role and therapeutic value.Archives of dermatological research · 2025Review
- Accurate identification of primary site in tumors of unknown origin (TUO) using DNA methylation.NPJ precision oncology · 2025Article
- Network-based analysis of heterogeneous patient-matched brain and extracranial melanoma metastasis pairs reveals three homogeneous subgroups.Computational and structural biotechnology journal · 2024Article
- DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.JCO precision oncology · 2024Article
- Personalized identification and characterization of genome-wide gene expression differences between patient-matched intracranial and extracranial melanoma metastasis pairs.Acta neuropathologica communications · 2024Article
- Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells.Cancers · 2024Review
- Integrating DNA methylation and gene expression data in a single gene network using the iNETgrate package.Scientific reports · 2023Article
- "iNETgrate": integrating DNA methylation and gene expression data in a single gene network.Research square · 2023Article
- Growth exponents reflect evolutionary processes and treatment response in brain metastases.NPJ systems biology and applications · 2023Article
- Emerging Biomarkers for Diagnosis, Prevention and Treatment of Brain Metastases-From Biology to Clinical Utility.Diseases (Basel, Switzerland) · 2022Review
- The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma.BMC cancer · 2022Article
- Epigenetics Regulates Antitumor Immunity in Melanoma.Frontiers in immunology · 2022Review
- Methylation Markers in Cutaneous Melanoma: Unravelling the Potential Utility of Their Tracking by Liquid Biopsy.Cancers · 2021Review
- Article
- Genomic and experimental evidence that ALKiScience · 2021Article
- Article
- Bona Fide Tumor Suppressor Genes Hypermethylated in Melanoma: A Narrative Review.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 3 countries.
Diego M MarzeseDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Richard A ScolyerDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Maria RoquéDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Laura M Vargas-RoigDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Jamie L HuynhDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
James S WilmottDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Rajmohan MuraliDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Michael E BucklandDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Garni BarkhoudarianDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
John F ThompsonDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Donald L MortonDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Daniel F KellyDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Dave S B HoonDepartment of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California (D.M.M., J.L.H., D.S.B.H.); Department of Tissue Oncology and Diagnostic Pathology (R.A.S., M.E.B., J.F.T.) and Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, Australia (J.F.T.); Sydney Medical School, The University of Sydney, Sydney, Australia (R.A.S., J.S.W., M.E.B., J.F.T.); Melanoma Institute Australia, Sydney, Australia (R.A.S., J.S.W.); Cellular and Molecular Biology Laboratory, Institute of Histology and Embryology, Mendoza, Argentina (M.R.); Tumor Biology Laboratory, Institute of Medicine and Experimental Biology of Cuyo, Mendoza, Argentina (L.M.V.-R.); Department of Pathology (R.M.), Center for Molecular Oncology (R.M.), and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York (R.M.); Division of Surgical Oncology, John Wayne Cancer Institute, Santa Monica, California (D.L.M.); Brain Tumor Center, Saint John's Health Center, Santa Monica, California (G.B., D.F.K.).
Instituto de Histología y Embriología de Mendoza · ARMelanoma Institute Australia · AUMemorial Sloan Kettering Cancer Center · USMolecular Oncology (United States) · USInstituto de Medicina y Biología Experimental de Cuyo · ARSaint John's Health Center · USUniversity of Sydney · AU
Funding
SURGICAL ONCOLOGY WITH COMBINATION THERMO-CHEMOTHERAPYP01CA029605 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COCHRAN, ALISTAIR JOHN · 1985 to 2013
$75.2MIdentification of Melanoma Brain Metastasis Tumor BiomarkersR01CA167967 · NCI · SAINT JOHN'S CANCER INSTITUTE · PI HOON, DAVE S B · 2013 to 2017
$1.9MNCI NIH HHS P01 CA029605NCI NIH HHS R01 CA167967
Abstract
backgroundThe brain is a common target of metastases for melanoma patients. Little is known about the genetic and epigenetic alterations in melanoma brain metastases (MBMs). Unraveling these molecular alterations is a key step in understanding their aggressive nature and identifying novel therapeutic targets.
methodsGenome-wide DNA methylation analyses of MBMs (n = 15) and normal brain tissues (n = 91) and simultaneous multigene DNA methylation and gene deletion analyses of metastatic melanoma tissues (99 MBMs and 43 extracranial metastases) were performed. BRAF and NRAS mutations were evaluated in MBMs by targeted sequencing.
resultsMBMs showed significant epigenetic heterogeneity. RARB, RASSF1, ESR1, APC, PTEN, and CDH13 genes were frequently hypermethylated. Deletions were frequently detected in the CDKN2A/B locus. Of MBMs, 46.1% and 28.8% had BRAF and NRAS missense mutations, respectively. Compared with lung and liver metastases, MBMs exhibited higher frequency of CDH13 hypermethylation and CDKN2A/B locus deletion. Mutual exclusivity between hypermethylated genes and CDKN2A/B locus deletion identified 2 clinically relevant molecular subtypes of MBMs. CDKN2A/B deletions were associated with multiple MBMs and frequently hypermethylated genes with shorter time to brain metastasis.
conclusionsMelanoma cells that colonize the brain harbor numerous genetically and epigenetically altered genes. This study presents an integrated genomic and epigenomic analysis that reveals MBM-specific molecular alterations and mutually exclusive molecular subtypes.
Indexed as
DNA MethylationGene DeletionAdultAgedAged, 80 and overBrain NeoplasmsCohort StudiesEpigenesis, GeneticFemaleFollow-Up StudiesHumansLiver NeoplasmsLung NeoplasmsMaleMelanomaMiddle AgedTumor Suppressor Proteinscancer progressiongene deletiongenome-wide DNA methylationmelanoma brain metastasis
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.